Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases
The tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/4/896 |
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| author | Hamid Mostafavi Abdolmaleky Marian Martin Jin-Rong Zhou Sam Thiagalingam |
| author_facet | Hamid Mostafavi Abdolmaleky Marian Martin Jin-Rong Zhou Sam Thiagalingam |
| author_sort | Hamid Mostafavi Abdolmaleky |
| collection | DOAJ |
| description | The tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However, until recently, the impact of non-neuronal brain cells, which arises due to cell-type-specific alterations, has not been adequately scrutinized; this is because of the absence of techniques that directly evaluate their functionality. With the emergence of single-cell technologies, such as RNA sequencing (RNA-seq) and other novel techniques, various studies have now started to uncover the cell-type-specific expression and DNA methylation regulation of many genes (e.g., <i>TREM2</i>, <i>MECP2</i>, <i>SLC1A2</i>, <i>TGFB2</i>, <i>NTRK2</i>, <i>S100B</i>, <i>KCNJ10,</i> and <i>HMGB1</i>, and several complement genes such as <i>C1q</i>, <i>C3</i>, <i>C3R</i>, and <i>C4</i>) in the non-neuronal brain cells involved in the pathogenesis of mental diseases. Additionally, several lines of experimental evidence indicate that inflammation and inflammation-induced oxidative stress, as well as many insidious/latent infectious elements including the gut microbiome, alter the expression status and the epigenetic landscapes of brain non-neuronal cells. Here, we present supporting evidence highlighting the importance of the contribution of the brain’s non-neuronal cells (in particular, microglia and different types of astrocytes) in the pathogenesis of mental diseases. Furthermore, we also address the potential impacts of the gut microbiome in the dysfunction of enteric and brain glia, as well as astrocytes, which, in turn, may affect neuronal functions in mental disorders. Finally, we present evidence that supports that microbiota transplantations from the affected individuals or mice provoke the corresponding disease-like behavior in the recipient mice, while specific bacterial species may have beneficial effects. |
| first_indexed | 2024-03-11T04:59:34Z |
| format | Article |
| id | doaj.art-f447e84e3e1d45a793b137b63fe95bda |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T04:59:34Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f447e84e3e1d45a793b137b63fe95bda2023-11-17T19:24:06ZengMDPI AGGenes2073-44252023-04-0114489610.3390/genes14040896Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental DiseasesHamid Mostafavi Abdolmaleky0Marian Martin1Jin-Rong Zhou2Sam Thiagalingam3Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USADepartment of Neurology, Albert Einstein College of Medicine, New York, NY 10461, USADepartment of Surgery, Nutrition/Metabolism Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USAThe tissue-specific expression and epigenetic dysregulation of many genes in cells derived from the postmortem brains of patients have been reported to provide a fundamental biological framework for major mental diseases such as autism, schizophrenia, bipolar disorder, and major depression. However, until recently, the impact of non-neuronal brain cells, which arises due to cell-type-specific alterations, has not been adequately scrutinized; this is because of the absence of techniques that directly evaluate their functionality. With the emergence of single-cell technologies, such as RNA sequencing (RNA-seq) and other novel techniques, various studies have now started to uncover the cell-type-specific expression and DNA methylation regulation of many genes (e.g., <i>TREM2</i>, <i>MECP2</i>, <i>SLC1A2</i>, <i>TGFB2</i>, <i>NTRK2</i>, <i>S100B</i>, <i>KCNJ10,</i> and <i>HMGB1</i>, and several complement genes such as <i>C1q</i>, <i>C3</i>, <i>C3R</i>, and <i>C4</i>) in the non-neuronal brain cells involved in the pathogenesis of mental diseases. Additionally, several lines of experimental evidence indicate that inflammation and inflammation-induced oxidative stress, as well as many insidious/latent infectious elements including the gut microbiome, alter the expression status and the epigenetic landscapes of brain non-neuronal cells. Here, we present supporting evidence highlighting the importance of the contribution of the brain’s non-neuronal cells (in particular, microglia and different types of astrocytes) in the pathogenesis of mental diseases. Furthermore, we also address the potential impacts of the gut microbiome in the dysfunction of enteric and brain glia, as well as astrocytes, which, in turn, may affect neuronal functions in mental disorders. Finally, we present evidence that supports that microbiota transplantations from the affected individuals or mice provoke the corresponding disease-like behavior in the recipient mice, while specific bacterial species may have beneficial effects.https://www.mdpi.com/2073-4425/14/4/896epigeneticDNA methylationgliaastrocytemicrobiome |
| spellingShingle | Hamid Mostafavi Abdolmaleky Marian Martin Jin-Rong Zhou Sam Thiagalingam Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases Genes epigenetic DNA methylation glia astrocyte microbiome |
| title | Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases |
| title_full | Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases |
| title_fullStr | Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases |
| title_full_unstemmed | Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases |
| title_short | Epigenetic Alterations of Brain Non-Neuronal Cells in Major Mental Diseases |
| title_sort | epigenetic alterations of brain non neuronal cells in major mental diseases |
| topic | epigenetic DNA methylation glia astrocyte microbiome |
| url | https://www.mdpi.com/2073-4425/14/4/896 |
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